A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Temodar Side Effects, and Drug Interactions - Temozolomide
Temodar Side Effects, and Drug Interactions - Temozolomide
SIDE EFFECTS
Tables 1 and 2 show the
incidence of adverse
events in the 158 patients in the Anaplastic Astrocytoma study for
whom data are available. In
the absence of a control
group, it is not clear in many cases whether these events should
be attributed to temozolomide or the patients' underlying conditions,
but nausea, vomiting,
fatigue and hematologic
effects appear to be clearly drug-related. The most frequently occurring
side effects were nausea,
vomiting, headache
and fatigue. The adverse events were usually NCI Common Toxicity
Criteria (CTC) Grade 1 or 2 (mild to moderate in severity) and were
self-limiting, with nausea
and vomiting readily
controlled with antiemetics. The incidence
of severe nausea and
vomiting (CTC grade
3 or 4) was 10% and 6%, respectively. Myelosuppression (thrombocytopenia
and neutropenia) was the dose-limiting adverse event. It usually
occurred within the first few cycles of therapy
and was not cumulative.
Myelosuppression occurred late in the treatment
cycle and returned to
normal, on average,
within 14 days of nadir counts. The median
nadirs occurred at 26 days for platelets [range 21-40 days] and
28 days for neutrophils [range 1-44 days]. Only 14% (22/158) of
patients had a neutrophil
nadir and 20% (32/158) of patients had a platelet
nadir which may have delayed the start of the next cycle. (See WARNINGS).
Less than 10% of patients required hospitalization, blood
transfusion or discontinuation
of therapy due to myelosuppression.
In clinical trial
experience with 110-111
women and 169-174 men (depending on measurements), there were higher
rates of Grade 4 neutropenia
(ANC < 500 cells/µL) thrombocytopenia
(< 20,000 cells/µL) in women than men in the first cycle
of therapy: (12% versus 5% and 9% versus 3%, respectively).
In the entire Safety
database for which hematologic data exist (N= 932), 7% (4/61) and
9.5% (6/63) of patients over age
70 experienced Grade 4 neutropenia or thrombocytopenia
in the first cycle, respectively. For patients less than or equal
to age 70, 7% (62/871) and
5.5% (48/879) experienced Grade 4 neutropenia
or thrombocytopenia
in the first cycle, respectively.
|
Table 1
|
Adverse Events in the Anaplastic Astrocytoma
Trial
(³5%)
|
|
No. (%) of TEMODAR Patients (N=158)
|
|
All Events
|
Grade 3/4
|
|
Any Adverse Event
|
153 (97)
|
79 (50)
|
|
Body as a Whole
|
|
Headache
|
65 (41)
|
10 (6)
|
|
Fatigue
|
54 (34)
|
7 (4)
|
|
Asthenia
|
20 (13)
|
9 (6)
|
|
Fever
|
21 (13)
|
3 (2)
|
|
Back pain
|
12 (8)
|
4 (3)
|
|
Cardiovascular
|
|
Edema peripheral
|
17 (11)
|
1 (1)
|
|
Central and Peripheral Nervous System
|
|
Convulsions
|
36 (23)
|
8 (5)
|
|
Hemiparesis
|
29 (18)
|
10 (6)
|
|
Dizziness
|
19 (12)
|
1 (1)
|
|
Coordination abnormal
|
17 (11)
|
2 (1)
|
|
Amnesia
|
16 (10)
|
6 (4)
|
|
Insomnia
|
16 (10)
|
0
|
|
Paresthesia
|
15 (9)
|
1 (1)
|
|
Somnolence
|
15 (9)
|
5 (3)
|
|
Paresis
|
13 (8)
|
4 (3)
|
|
Urinary incontinence
|
13 (8)
|
3 (2)
|
|
Ataxia
|
12 (8)
|
3 (2)
|
|
Dysphasia
|
11 (7)
|
1 (1)
|
|
Convulsions local
|
9 (6)
|
0
|
|
Gait abnormal
|
9 (6)
|
1 (1)
|
|
Confusion
|
8 (5)
|
0
|
|
Endocrine
|
|
Adrenal hypercorticism
|
13 (8)
|
0
|
|
Gastro-Intestinal System
|
|
Nausea
|
84 (53)
|
16 (10)
|
|
Vomiting
|
66 (42)
|
10 (6)
|
|
Constipation
|
52 (33)
|
1 (1)
|
|
Diarrhea
|
25 (16)
|
3 (2)
|
|
Abdominal pain
|
14 (9)
|
2 (1)
|
|
Anorexia
|
14 (9)
|
1 (1)
|
|
Metabolic
|
|
Weight increase
|
8 (5)
|
0
|
|
Musculo-Skeletal System
|
|
Myalgia
|
8 (5)
|
|
|
Psychiatric Disorders
|
|
Anxiety
|
11 (7)
|
1 (1)
|
|
Depression
|
10 (6)
|
0
|
|
Reproductive Disorders
|
|
Breast pain,
female
|
4 (6)
|
|
|
Resistance Mechanism Disorders
|
|
Infection viral
|
17 (11)
|
0
|
|
Respiratory System
|
|
Upper respiratory
tract
|
13 (8)
|
0
|
|
infection
|
|
|
|
Pharyngitis
|
12 (8)
|
0
|
|
Sinusitis
|
10 (6)
|
0
|
|
Coughing
|
8 (5)
|
0
|
|
Skin and Appendages
|
|
Rash
|
13 (8)
|
0
|
|
Pruritus
|
12 (8)
|
2 (1)
|
|
Urinary System
|
|
Urinary tract
infection
|
12 (8)
|
0
|
|
Micturition increased
|
9 (6)
|
0
|
|
frequency
|
|
|
|
Vision
|
|
Diplopia
|
8 (5)
|
0
|
|
Vision Abnormal *
|
8 (5)
|
|
|
* Blurred vision, visual
deficit, vision changes, vision
troubles
|
|
Table 2
|
Adverse Hematologic Effects (Grade
3-4) in the Anaplastic Astrocytoma
Trial
|
|
|
Temodal a
|
|
Hemoglobin
|
7/158 (4%)
|
|
Neutrophils
|
20/142 (14%)
|
|
Platelets
|
29/156 (19%)
|
|
WBC
|
18/158 (11%)
|
|
a: Change from grade
0-2 at baseline to grade
3 or 4 during treatment.
|
DRUG INTERACTIONS
Administration of valproic acid
decreases oral clearance
of temozolomide by about 5%. The clinical
implication of this effect
is not known.
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